Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Point mutations in ras genes resulting in substitutions of amino acid Gly in positions 12 and 13, and Gln in position 61 of the ras gene product p21, are commonly found in human tumors. Peptides derived from aberrant p21 may elicit a tumor specific T cell response, provided that these peptides can bind to HLA molecules of the tumor and the patient has T cells able to recognize the corresponding peptide-HLA complex. Here we report that CD4+ T cells of memory type (CD45RO+) from a patient with a follicular thyroid carcinoma respond against a synthetic peptide derived from aberrant p21 ras having a Gln-->Leu substitution at position 61. Such responses were not observed when T cells from healthy volunteers or cancer patients where this mutation does not usually occur were stimulated with this peptide. The responding T cells did not cross-react with the corresponding peptide derived from native p21 ras nor did they recognize peptides carrying other substitutions in position 61. T cells clones were generated which recognized this Leu61 peptide when presented by HLA-DQ8 molecules. These T cell clones also recognized the corresponding intact p21 ras protein. By using several different synthetic peptides, a peptide with optimal stimulatory capacity was defined. Performing polymerase chain reaction and oligonucleotide probing we were, however, not able to detect the p21 ras gene encoding the Gln-->Leu substitution in DNA from tumor biopsies from the patient. This may indicate that tumor cells harboring the mutation leading to the Gln-->Leu substitution had been eliminated and that tumor progression was due to cells that had deleted the mutated ras gene. The finding that ras derived peptides and recombinant mutated p21 ras are immunogenic in man may form the basis for the development of cancer immunotherapy based on synthetic oncogene derived peptides.
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PMID:Memory T cells of a patient with follicular thyroid carcinoma recognize peptides derived from mutated p21 ras (Gln-->Leu61). 128 32

Metastatic prostate carcinomas in autopsy cases from three populations 49 cases of indigenous Japanese, 29 cases of Japanese Americans and 14 from whites in Hawaii) were compared in terms of their clinicopathological, immunohistochemical (tenascin and ras p21) and lectin binding (Helix Pomatia antigen, HPA) properties. Only the clinicopathological features were analyzed in the cases of whites in Hawaii. The results indicate that poorly differentiated carcinoma is less common, whereas distant metastasis is more frequent, in indigenous Japanese. Some of the Japanese-American cases with poorly differentiated carcinomas did not show any distant metastases. HPA and ras p21 expression are more common, but tenascin is less common in indigenous Japanese. HPA expression is more common in cases with metastasis, especially with metastasis to the bone and other organs, than nonmetastatic cases. Prostatic cancer cases in indigenous Japanese were more aggressive biologically than those in Japanese Americans, but no phenotypic differences were seen relevant to the presence or absence of bone metastases.
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PMID:Comparative study of prostatic carcinoma bone metastasis among Japanese in Japan and Japanese Americans and whites in Hawaii. 128 3

RAS protein (p21 ras) requires farnesyl (an intermediate of cholesterol synthesis) for activation. Activating mutations of K-ras gene have been detected in most human pancreatic adenocarcinomas. In the present study, the effect of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A, the rate-limiting enzyme of cholesterol synthesis, on the growth of five pancreatic cancer cell lines (human-CAV, MIA Paca2, CAPAN2 and PANC1, and hamster-H2T) in vitro and of two cell lines (CAV and H2T) in vivo was examined. Inhibition of cell growth was observed with lovastatin doses at or above 2.5 micrograms/mL for H2T, CAV, MIA Paca2, and CAPAN2 or 10 micrograms/mL in PANC1. The H2T cell line was studied further to determine the reversibility of growth inhibition. Mevalonic acid (1 mmol/L) reversed lovastatin-induced inhibition of cell growth if it was added with lovastatin (2.5 micrograms/mL). Similarly, removal of lovastatin from the medium within 24 hours after treatment allowed recovery of cell growth. The effect of lovastatin on cell growth was irreversible after 48 hours of exposure. The survival fraction of H2T cells was markedly decreased by 1- or 24-hour exposure to 75 micrograms/mL but not to doses ranging from 0.5 to 60 micrograms/mL of lovastatin. Growth of pancreatic carcinoma xenografts (CAV and H2T) in nude mice was inhibited by a subcutaneous infusion of lovastatin (50 micrograms/h). These results indicate that mevalonic acid or a metabolite in the cholesterol synthesis pathway is necessary for growth of pancreatic cancer cells and suggest that lovastatin should be further examined as a potential therapeutic agent for pancreatic cancer.
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PMID:Inhibition of pancreatic adenocarcinoma cell growth by lovastatin. 149 46

Although regeneration-competent newts like Notophthalmus viridescens have been reported to be resistant to carcinogenesis, we have been able to induce transplantable epidermal squamous cell carcinomas with 10-20% incidence by implanting 20-methylcholanthrene s.c. into the scapular region, a tissue that cannot regenerate. As soon as 1 week after exposure to this carcinogen, malignant cells were present in the treated skin, and after 4 weeks, macroscopic tumors of infiltrating squamous carcinoma cells positive for Type IV collagenase and/or rasHa p21 had dissolved areas of the epidermal basement membrane and colonized the dermis. Analysis of Ki-67 expression revealed that these tumors grow via a high growth fraction rather than a short cell cycle time. Morphological and immunohistochemical analyses showed that these tumors caricature the biology of the renewing epidermis: the presence of basal-like cells; differentiating cells; apoptotic cells; and keratinized horn pearls with an exaggerated or overabundant stem cell compartment as compared to the differentiated cell compartment. Immunochemical analyses indicated that the squamous carcinomas arose from the epidermis rather than the mucous glands. Thus, the principle that malignant tumors caricature the process of tissue renewal originally established in rodent tumors appears to be valid down the phylogenetic tree at least to regeneration-competent amphibia. Such a broad conservation indicates that the caricature principle also holds in human tumors.
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PMID:Newt squamous carcinoma proves phylogenetic conservation of tumors as caricatures of tissue renewal. 151 43

Twenty-three clinically silent prostatic carcinomas discovered in Japanese men at autopsy were surveyed for ras proto-oncogene mutations by mutation-specific oligonucleotide probe hybridization after polymerase chain reaction (PCR) amplification from a section of formalin-fixed, paraffin-embedded tissue. Six of the 22 that were satisfactory amplified contained activating point mutations in codon 12 of K-ras, a significantly higher frequency than has been reported in patients with clinically advanced disease in the United States. Of the six cases with activating point mutations in codon 12 of K-ras, one had a GGT----GAT transition, four had GGT----GTT transversions, and one had both GGT----GAT and GGT----GTT mutations. Sections from the same tissues were immunohistochemically stained with an anti-ras p21 antibody. Carcinoma cells stained for ras p21 to some degree in 13 cases. Immunohistochemically detectable expression of p21 was always focal and was not necessarily associated with K-ras mutation. K-ras oncogene activation in prostatic carcinoma appears to merit additional study as a significant event in the pathogenesis of this neoplasm.
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PMID:K-ras activation and ras p21 expression in latent prostatic carcinoma in Japanese men. 156 75

Mapping specimens of 6 cases of ulcerative colitis included adenocarcinoma invaded into submucosa (invasive carcinoma) were made and immunohistochemical quantitative analysis of ras p21, an oncogene product and secretory component were examined in invasive carcinoma, severe and moderate dysplasia of ulcerative colitis. Large intestinal carcinoma invaded into submucosa, colonic adenoma and normal mucosa were examined as the control. Index values of Staining Density (ISD) and of Staining Gland (ISG) of ras p21 demonstrated significantly higher values in invasive carcinoma, severe and moderate dysplasia of ulcerative colitis than adenoma (P less than 0.01). ISG of secretory component in moderate dysplasia and adenoma showed significantly high value compared with severe dysplasia and invasive carcinoma of ulcerative colitis (P less than 0.05). The collective evidence indicates that severe dysplasia falls into the same category with invasive carcinoma of ulcerative colitis and may be defined as carcinoma in situ. Moderate dysplasia was also defined as carcinoma in situ or borderline lesion.
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PMID:[Morphological and immunohistochemical quantitative analysis of dysplasia in ulcerative colitis. II. Immunohistochemical quantitative analysis]. 157 4

In an attempt to clarify the relationship between ras oncogene expression and the clinico-pathological features of malignant and pre-malignant lesions of the stomach we undertook the immunohistochemical study of the expression of ras gene p21 product in a series of eighty gastric carcinomas and their respective adjacent mucosas. In two cases the mRNA of Ha-ras was also studied by in situ hybridization. The majority of gastric carcinomas as well as their adjacent non-neoplastic mucosas expressed ras gene product. There was a significant relationship between the expression of ras gene p21 product and the morphologic pattern of the tumours. An enhanced ras expression was found in several conditions regarded as precursor lesions of intestinal and/or diffuse types of gastric carcinoma (dysplasia, foveolar hyperplasia and even the neck zone of normal-appearing gastric glands, namely in the mucosa adjacent to diffuse carcinomas). Ras expression was actually more prominent in most of these conditions than in their respective adjacent carcinomas. No significant relationship was found between ras expression and invasiveness of the wall, nodal metastases and venous invasion.
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PMID:Immunohistochemical analysis of ras oncogene p21 product in human gastric carcinomas and their adjacent mucosas. 162 89

For the purpose of demonstrating the relationship between the expression of ras oncogene p21 protein and clinico-pathological characteristics which reflected the prognosis, 253 women with breast cancer who underwent mastectomy were analyzed. Ras p21 was detected in 133 (52.6%). In histological types, scirrhous carcinomas were more often ras p21-positive, and papillo-tubular carcinoma were usually negative. And histological grade was significantly correlated with ras p21. The degrees of invasion to fat tissues and infiltration into lymphatic vessels were also significantly correlated with ras p21. Tumors with lymph node metastases expressed higher levels of ras p21 than nonmetastasizing tumors in smaller tumors, especially in papillo-tubular carcinomas. And patients with elevated ras expression tended to have a poor prognosis. These results suggested that an elevated ras expression may play an important role in the development of aggressive tumors.
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PMID:[Expression of ras oncogene p21 in relation to prognostic factors of human breast cancer]. 165 90

Pathological diagnosis of hepatic tumors is sometimes difficult when performed with only routine examinations such as Hematoxylin and Eosin (H.E.) stain. The diagnostic usefulness of KM01 was compared to that of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA19-9 and ras p21 in this immunohistochemical study. AFP was positive in about half of the cases of hepatocellular carcinoma and hepatoblastoma, and AFP-positive cells were frequently found at the periphery of acini in both diseases. Absorbed CEA stain was mostly negative in hepatocellular carcinoma, but was positive in the cells of mixed hepatocellular and cholangiocellular carcinoma (MHCC) and metastatic liver cancer, especially in their cytoplasm. CA19-9 immunostaining was completely negative, and was only 3% positive in hepatocellular carcinoma. KM01 stain was positive in about half of the cases of hepatocellular carcinoma, hepatoblastoma and MHCC. It was positive in proliferated bile ducts around the capsule in the former two diseases but positive in the tumor cell of both parts of the cytoplasm in the latter. The histological positivity of ras p21 was high in all tumor cells of these three types of tumors. Negative absorbed CEA and KM01 in pseudoglandular hepatocellular carcinoma differentiated from MHCC and metastatic liver cancer. However these tumor markers were occasionally positive and nonspecific in cancer-like lesions, implying no advantage for differential diagnosis between hepatocellular carcinoma and apparent cancer-like lesions. The above results demonstrate that AFP, CEA and KM01 are effective for differentiating hepatocellular carcinoma among various hepatic tumors.
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PMID:Immunohistochemical study on hepatic tumors--KM01 stains compared with AFP, CEA, CA19-9 and RAS P21. 171 40

Immunocytochemistry with monoclonal antibody Y13-259 demonstrated p21 ras in paraffin sections of breast tissue from 171 women: 85 with invasive breast carcinoma, 14 with non-invasive carcinoma and 72 with benign changes only. Many different tissue elements contributed to ras expression. Semiquantitative assessment showed that intensity of immunostaining in the normal epithelium of large ducts, small extralobular ducts and terminal duct lobular units (TDLU) was usually exceeded by that of myoepithelial cells. Vascular smooth muscle and apocrine epithelium also stained strongly, but the flat epithelial cells lining cysts did not express detectable p21 ras. There was a progressive increase from normal epithelium through epithelial hyperplasia of usual type and atypical hyperplasia to carcinoma in situ, without further increase in invasive carcinoma. Expression in carcinomas was inversely related to oestrogen receptor content but independent of the prognosis-associated variables of size, histological type, vascular invasion or lymph node metastasis.
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PMID:Ras p21 in breast tissue: associations with pathology and cellular localisation. 173 41


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